The ability to selectively inhibit the growth of a subset of cells in a mixture of cells has many applications in culture and in vivo. Where two sets of cells have distinguishing characteristics, such as tumor cells which require expression of one or more genes, which are not expressed in normal cells or only expressed at a low level, there is substantial interest in being able to selectively inhibit the proliferation of the tumor cells. Where groups of cells are differentiating, and at one level of differentiation, expression of a particular gene is required, the ability to inhibit the expression of that gene can be of interest. Where cells are infected by viruses, parasite or mycoplasmas, the selective ability to inhibit the growth of the virus or mycoplasma can be an important goal.
In the studies of metabolic processes, differentiation, activation, and the like, there are many situations where it is desirable to be able to selectively inhibit the transcription of a particular gene. In this way, one can study the effect of a reduction in the transcription of the gene and expression of the gene on the phenotype of the cell. In the extensive efforts to understand embryonic and fetal development, to define segmental polarity genes and their function, there is also interest in being able to selectively inhibit particular genes during various phases of the development of the fetus.
As in the case of the studies in culture, selective inhibition of particular genes can also be of interest in vivo. In many situations, cellular proliferation can be injurious to the host. The proliferation can be as a result of neoplasia, inflammation, or other process where increased number of cells has an adverse effect upon the health of the host.
There is, therefore, substantial interest in finding techniques and reagents which allow for selective inhibition of particular genes, so as to control intracellular molecular processes.
Relevant Literature
WO93/05178 provides an extensive description of double D-loop formation, with an extended bibliography of references. Sena and Zarling, (1993) Nature Genetics 3:365-372 and Revet, Sena and Zarling, J. Mol. Biol.232:779-791 describe double D-loop formation. Golub et al., (1992) Nucleic Acids Res. 20:3121-5; Golub et al., (1993) Proc. Natl. Acad. Sci. USA. 90:7186-90; Ferrin and Camerini-Otero, (1991) Science 254:1494-7.; Koob et al. (1992) Nucleic Acids Res. 20:5831-6; Revet et al. (1993) J. Mol. Biol. 232:779-91; Sena (1993) Nature Genetics 3:365-371 and Jayasena and Jonnston (1993) J. Molec Biol. 230:1015-1024.